U.S. patent application number 13/884051 was filed with the patent office on 2013-09-12 for oral care product and methods of use and manufacture thereof.
This patent application is currently assigned to Colgate-Palmolive Company. The applicant listed for this patent is Evangelia S. Arvanitidou, Christine Cuiule, Rensl Dillon, Catherine Lewus, Sarita Mello, Jason Nesta, Kimdra Smith-Webster, Gregory Szewczyk. Invention is credited to Evangelia S. Arvanitidou, Christine Cuiule, Rensl Dillon, Catherine Lewus, Sarita Mello, Jason Nesta, Kimdra Smith-Webster, Gregory Szewczyk.
Application Number | 20130236400 13/884051 |
Document ID | / |
Family ID | 44590255 |
Filed Date | 2013-09-12 |
United States Patent
Application |
20130236400 |
Kind Code |
A1 |
Lewus; Catherine ; et
al. |
September 12, 2013 |
Oral Care Product and Methods of Use and Manufacture Thereof
Abstract
This invention relates to a dual phase mouthwash comprising a
hydrophilic phase, a hydrophobic phase, and a hydrotrope, wherein
the hydrophilic phase comprises an effective amount of a
preservative selected from methylisothiazolinone, sodium benzoate,
potassium sorbate, and combinations thereof, as well as to methods
of using and of making such compositions.
Inventors: |
Lewus; Catherine; (Denville,
NJ) ; Szewczyk; Gregory; (Flemington, NJ) ;
Mello; Sarita; (North Brunswick, NJ) ; Smith-Webster;
Kimdra; (Williamstown, NJ) ; Nesta; Jason;
(Cedar Knolls, NJ) ; Dillon; Rensl; (Ewing,
NJ) ; Arvanitidou; Evangelia S.; (Princeton, NJ)
; Cuiule; Christine; (Mount Laurel, NJ) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
Lewus; Catherine
Szewczyk; Gregory
Mello; Sarita
Smith-Webster; Kimdra
Nesta; Jason
Dillon; Rensl
Arvanitidou; Evangelia S.
Cuiule; Christine |
Denville
Flemington
North Brunswick
Williamstown
Cedar Knolls
Ewing
Princeton
Mount Laurel |
NJ
NJ
NJ
NJ
NJ
NJ
NJ
NJ |
US
US
US
US
US
US
US
US |
|
|
Assignee: |
Colgate-Palmolive Company
New York
NY
|
Family ID: |
44590255 |
Appl. No.: |
13/884051 |
Filed: |
November 12, 2010 |
PCT Filed: |
November 12, 2010 |
PCT NO: |
PCT/US10/56514 |
371 Date: |
May 8, 2013 |
Current U.S.
Class: |
424/52 ; 424/49;
424/56; 424/57 |
Current CPC
Class: |
A61K 8/36 20130101; A61K
8/37 20130101; A61K 8/31 20130101; A61K 8/21 20130101; A61K 8/49
20130101; A61K 8/92 20130101; A61K 8/368 20130101; A61K 8/345
20130101; A61K 8/03 20130101; A61P 1/02 20180101; A61K 8/55
20130101; A61Q 11/00 20130101 |
Class at
Publication: |
424/52 ; 424/49;
424/56; 424/57 |
International
Class: |
A61K 8/92 20060101
A61K008/92; A61Q 11/00 20060101 A61Q011/00; A61K 8/49 20060101
A61K008/49; A61K 8/55 20060101 A61K008/55; A61K 8/368 20060101
A61K008/368; A61K 8/21 20060101 A61K008/21 |
Claims
1. A dual phase mouthwash comprising a hydrophilic phase, a
hydrophobic phase, a hydrotrope, and a preservative wherein the
preservative comprises (i) sodium benzoate and (ii) potassium
sorbate and/or methylisothiazolinone and wherein the mouthwash
comprises (a) 0.05%-0.5% sodium benzoate and (b) 0.05%-0.2%
potassium sorbate and/or 0.0005%-0.01% MIT.
2. The mouthwash of claim 1 wherein the hydrotrope component
comprises glycerin and/or propylene glycol.
3. The mouthwash of claim 1 wherein the hydrophobic phase comprises
an oil selected from isopropyl myristate, mineral oil, an edible
oil, and combinations thereof.
4. The mouthwash of claim 1 wherein the hydrophilic phase comprises
the hydrotrope component.
5. The mouthwash of claim 1 wherein the hydrophilic phase further
comprises cetylpyridinium chloride, e.g., in an amount of from
0.01-0.1%, e.g., 0.05%.
6. The mouthwash of claim 1 further comprising a pyrophosphate.
7. The mouthwash of claim 1 further comprising a synthetic anionic
polymeric polycarboxylate.
8. The mouthwash of claim 1 further comprising a fluoride ion
source.
9. The mouthwash of claim 1 which is ethanol-free.
10. The mouthwash of claim 1 further comprising one or more of
humectants, flavorings, and surfactants.
11. The mouthwash of claim 1 wherein the hydrophilic phase
comprises an effective amount of the preservative.
12. A method to improve oral health comprising applying an
effective amount of the mouthwash of any of the preceding claims to
the oral cavity of a subject in need thereof to a. reduce or
inhibit formation of dental caries, b. reduce, repair or inhibit
early enamel lesions, c. reduce or inhibit demineralization and
promote remineralization of the teeth, d. reduce hypersensitivity
of the teeth, e. reduce or inhibit gingivitis, f. promote healing
of sores or cuts in the mouth, g. inhibit microbial biofilm
formation in the oral cavity, h. raise and/or maintain plaque pH at
levels of at least pH 5.5 following sugar challenge, i. reduce
plaque accumulation, j. treat, relieve or reduce dry mouth, k.
whiten teeth, l. enhance systemic health, including cardiovascular
health, m. reduce erosion of the teeth, n. to immunize the teeth
against cariogenic bacteria and their effects, and/or o. clean the
teeth and oral cavity.
13. A dual phase mouthwash according to claim 1 for use in a method
to a. reduce or inhibit formation of dental caries, b. reduce,
repair or inhibit early enamel lesions, c. reduce or inhibit
demineralization and promote remineralization of the teeth, d.
reduce hypersensitivity of the teeth, e. reduce or inhibit
gingivitis, f. promote healing of sores or cuts in the mouth, g.
inhibit microbial biofilm formation in the oral cavity, h. raise
and/or maintain plaque pH at levels of at least pH 5.5 following
sugar challenge, i. reduce plaque accumulation, j. treat, relieve
or reduce dry mouth, k. whiten teeth, l. enhance systemic health,
including cardiovascular health, m. reduce erosion of the teeth, n.
to immunize the teeth against cariogenic bacteria and their
effects, and/or o. clean the teeth and oral cavity.
14. The mouthwash of claim 4, wherein the hydrophobic phase
comprises an oil selected from isopropyl myristate, mineral oil, an
edible oil, and combinations thereof, the hydrotrope component
comprises glycerin and/or propylene glycol and the mouthwash is
ethanol-free.
Description
FIELD OF THE INVENTION
[0001] This invention relates to a preservative system for dual
phase mouthwash composition comprising (i) a hydrophilic phase
including a hydrotrope, (ii) a hydrophobic phase, and (iii) a
preservative selected from methylisothiazolinone, sodium benzoate,
and potassium sorbate and combinations thereof, as well as to
methods of using and of making these compositions.
BACKGROUND OF THE INVENTION
[0002] Because of their high water content, mouthwashes present
particular challenges in preventing microbial contamination. Dual
phase mouthwashes present particular challenges in that the
hydrophilic and hydrophobic phases should remain separated and faun
a temporary emulsion when mixed. The emulsion spontaneously reverts
back to the two original phases after rest, without the formation
of an emulsion. See, e.g., U.S. Patent Publication 20090311200, the
contents of which are incorporated herein by reference. Selection
of a preservative which is both effective and which does not impair
the physical properties of the dual phase formulation is not
trivial. Additionally, some preservatives negatively affect the
taste or aesthetics of the product. Finally, conventional agents
such as ethanol and paraben preservatives may be undesirable for
certain indications or in particular markets.
[0003] Accordingly, there is a need to identify improved
preservative agents for use in dual phase mouthwashes.
BRIEF SUMMARY OF THE INVENTION
[0004] It is now surprisingly discovered that dual phase
mouthwashes comprising (i) a hydrophilic phase including a
hydrotrope, (ii) a hydrophobic phase, and (iii) a preservative
selected from methylisothiazolinone, sodium benzoate, and potassium
sorbate and combinations thereof, are stable and effective.
[0005] The invention thus encompasses oral care compositions and
methods of using the same that are effective in inhibiting or
reducing the accumulation of plaque, reducing levels of acid
producing (cariogenic) bacteria, remineralizing teeth, and
inhibiting or reducing gingivitis. The invention also encompasses
compositions and methods to clean the oral cavity and provide
improved methods of promoting oral health and/or systemic health,
including cardiovascular health, e.g., by reducing potential for
systemic infection via the oral tissues.
[0006] The invention thus provides a mouthwash composition (a
Composition of the Invention), comprising (i) a hydrophilic phase
including a hydrotrope, (ii) a hydrophobic phase, and (iii) a
preservative selected from methylisothiazolinone, sodium benzoate,
potassium sorbate, and combinations thereof.
[0007] The Compositions of the Invention may comprise additional
ingredients, e.g., selected from one or more of water, surfactants,
solvents, vitamins, minerals, polymers, enzymes, humectants,
thickeners, additional antimicrobial agents, additional
preservatives, flavorings, colorings and/or combinations thereof.
In particular embodiments, the invention may comprise an
anti-calculus agent for example polyphosphate, e.g., pyrophosphate,
tripolyphosphate, or hexametaphosphate, e.g., in alkali, e.g.,
sodium or potassium salt faun, and/or may comprise a synthetic
anionic polymeric polycarboxylate, such as 1:4 to 4:1 copolymers of
maleic anhydride or acid with another polymerizable ethylenically
unsaturated monomer, for example a co-polymer of methyl vinyl
ether/maleic anhydride.
[0008] Effective amounts for the preservatives in the Compositions
of the Invention, separately or in combination, are, for example,
as follows, by weight: MIT: less than 0.1%, e.g., 0.0005-0.1%, e.g.
0.001%, 0.01% or 0.05%; sodium benzoate less than 1%, e.g.
0.1-0.5%, e.g., 0.11% or 0.44%; potassium sorbate less than 1%,
e.g. 0.05%-0.5%, e.g., 0.1%.
[0009] The invention further encompasses methods comprising
applying compositions effective upon application to the oral
cavity, e.g., rinsing the oral cavity, optionally in conjunction
with brushing, to (i) reduce or inhibit formation of dental caries,
(ii) reduce or inhibit demineralization and promote
remineralization of the teeth, (iii) reduce hypersensitivity of the
teeth, (iv) reduce or inhibit gingivitis, (v) promote healing of
sores or cuts in the mouth, (vi) reduce levels of acid producing
bacteria, (vii) to increase relative levels of arginolytic
bacteria, (viii) inhibit microbial biofilm formation in the oral
cavity, (ix) raise and/or maintain plaque pH at levels of at least
pH 5.5 following sugar challenge, (x) reduce plaque accumulation,
(xii) treat, relieve or reduce dry mouth, (xii) clean the teeth and
oral cavity (xiii) reduce erosion, (xiv) whiten teeth, (xv)
immunize the teeth against cariogenic bacteria; and/or (xvi)
promote systemic health, including cardiovascular health, e.g., by
reducing potential for systemic infection via the oral tissues.
DETAILED DESCRIPTION OF THE INVENTION
[0010] The invention thus provides, in a first embodiment, a dual
phase mouthwash (Composition 1.0), comprising [0011] a hydrophilic
phase including a hydrotrope, a hydrophobic phase, and an effective
amount of a preservative selected from methylisothiazolinone,
sodium benzoate, potassium sorbate, and combinations thereof. For
example, any of the following compositions: [0012] 1.0.1.
Composition 1.0 wherein the wherein hydrophobic and hydrophilic
phases spontaneously separate following mixing of the phases and
are substantially non-emulsified at room temperature one hour
following mixing. [0013] 1.0.2. Any of the foregoing compositions
wherein the hydrotrope component of the hydrophilic phase comprises
a polyglycol, a polyhydric alcohol, or a mixture thereof. [0014]
1.0.3. Any of the foregoing compositions wherein the hydrotrope
component comprises ethylene glycol, propylene glycol, glycerin,
diethylene glycol, di-propylene glycol, tripropylene glycol, xylene
glycol, 1,3-butylene glycol, 1,4-butylene glycol,
1,2,6-hexanetriol, sorbitol, xylitol, or a combination thereof.
[0015] 1.0.4. Any of the foregoing compositions wherein the
hydrotrope component comprises glycerin and/or propylene glycol.
[0016] 1.0.5. Any of the foregoing compositions wherein the
hydrotrope component comprises sorbitol. [0017] 1.0.6. Any of the
foregoing compositions wherein the hydrophobic phase comprises an
oil selected from isopropyl myristate, mineral oil, an edible oil,
and combinations thereof. [0018] 1.0.7. Any of the foregoing
compositions comprising from 1% to 90% by volume of the hydrophilic
phase. [0019] 1.0.8. Any of the foregoing compositions having a
15:85 hydrophobic to hydrophilic weight ratio. [0020] 1.0.9. Any of
the foregoing compositions wherein the hydrophilic phase comprises
the hydrotrope component. [0021] 1.0.10. Any of the foregoing
compositions which is substantially free of a cationic surfactant.
[0022] 1.0.11. Any of the foregoing compositions wherein the
preservatives are present, separately or in combination, in amounts
by weight: MIT: less than 0.1%, e.g., 0.0005-0.1%, e.g. 0.001%,
0.01% or 0.05%; sodium benzoate less than 1%, e.g. 0.1-0.5%, e.g.,
0.11% or 0.44%; potassium sorbate less than 1%, e.g. 0.05%-0.5%,
e.g., 0.1%. [0023] 1.0.12. The foregoing composition wherein the
preservative comprises sodium benzoate. [0024] 1.0.13. The
foregoing composition wherein the preservative comprises sodium
benzoate and potassium sorbate. [0025] 1.0.14. The foregoing
composition comprising (i) 0.05%-0.5% sodium benzoate and (ii)
0.05%-0.2% potassium sorbate and/or 0.0005%-0.01% MIT. [0026]
1.0.15. Any of the foregoing compositions wherein the hydrophilic
phase further comprises cetyl pyridinium chloride, e.g., in an
amount of from 0.01-0.1%, e.g., 0.05%. [0027] 1.0.16. Any of the
foregoing compositions wherein the hydrophilic phase further
comprises an acid, e.g. an organic acid, e.g., citric acid. [0028]
1.0.17. Any of the foregoing compositions further comprising an
anti-calculus agent for example polyphosphate, e.g., pyrophosphate,
tripolyphosphate, or hexametaphosphate, e.g., in salt form, e.g.,
sodium or potassium salt form, e.g., in an amount of from 0.1-3%.
[0029] 1.0.18. The foregoing composition wherein the anti-calculus
agent is a pyrophosphate selected from tetrasodium pyrophosphate
and tetrapotassium pyrophosphate and mixtures thereof. [0030]
1.0.19. The foregoing composition comprising 0.1 to 1% tetrasodium
pyrophosphate and 1-2% tetrapotassium pyrophosphate, e.g.
0.25-0.75% tetrasodium pyrophosphate and 1.0-1.5% tetrapotassium
pyrophosphate. [0031] 1.0.20. Any of the preceding compositions
comprising at least one polymer selected from polyethylene glycols;
synthetic anionic polymeric polycarboxylate, such as
polyvinylmethyl ether maleic acid copolymers; polysaccharides
(e.g., cellulose derivatives, for example carboxymethyl cellulose
or polysaccharide gums, for example xanthan gum or carrageenan
gum); and combinations thereof. [0032] 1.0.21. Any of the foregoing
compositions comprising a synthetic anionic polymeric
polycarboxylate, e.g., in an amount of 1-10%, e.g., 2.5-7.5%.
[0033] 1.0.22. The foregoing composition wherein the synthetic
anionic polymeric polycarboxylate is a 1:4 to 4:1 copolymer of
maleic anhydride or acid with another polymerizable ethylenically
unsaturated monomer, e.g. methyl vinyl ether/maleic anhydride
having a molecular weight (M.W.) of 30,000 to 5,000,000 daltons,
for example 1000 kD-3000 kD. [0034] 1.0.23. The foregoing
composition comprising a co-polymer of methyl vinyl ether/maleic
anhydride having the general structure
CH.sub.2--CH(OCH.sub.3)--CH(COOH)--CH(COOH) .sub.n, viscosity of CP
at 25.degree. C. of 1-3 kCP, e.g., 1.7.times.10.sup.3 CP, and
nominal molecular weight of 1000 kD-3000 kD, e.g.,
1.98.times.10.sup.6, for example in an amount by weight of 1-10%,
e.g., 5% [0035] 1.0.24. Any of the foregoing compositions which is
ethanol-free. [0036] 1.0.25. Any of the foregoing compositions
further comprising a basic amino acid in free or salt for, for
example arginine, for example in an amount of 0.1-3%, e.g. 0.8%,
[0037] 1.0.26. Any of the foregoing compositions further comprising
a soluble calcium salt, e.g., selected from calcium
glycerophosphate and salts of soluble carboxylic acids, and
mixtures thereof, e.g., wherein the calcium salt is selected from
calcium citrate, calcium malate, calcium lactate, calcium formate,
calcium fumarate, calcium gluconate, calcium lactate gluconate,
calcium aspartate, and calcium propionate, and mixtures thereof.
[0038] 1.0.27. Any of the preceding compositions further comprising
a fluoride source, e.g., a fluoride salt, for example sodium
fluoride, or wherein the fluoride is covalently bound to another
atom, e.g., a monofluorophosphate, for example sodium
monofluorophosphate, a fluorosilicate, e.g., sodium fluorosilicate
or ammonium fluorosilicate, or a fluorosulfate, e.g.,
hexafluorosulfate, amine fluoride and combinations thereof. [0039]
1.0.28. The preceding composition wherein the fluoride salt is
present in an amount to provide 100 to 250 ppm available fluoride.
[0040] 1.0.29. Any of the preceding compositions comprising sodium
fluoride in an amount of 0.01-0.1%, e.g., 0.05%. [0041] 1.0.30. Any
of the preceding compositions wherein the pH is between 5 and 6.5,
e.g. 5.5. [0042] 1.0.31. Any of the preceding compositions further
comprising an abrasive or particulate. [0043] 1.0.32. Any of the
preceding compositions comprising a nonionic surfactant, e.g., in
an amount of from 0.5-5%, for example 1-2%, selected from
polaxamers (e.g., polaxamer 407), polysorbates (e.g., polysorbate
20), polyoxyl hydrogenated castor oil (e.g., polyoxyl 40
hydrogenated castor oil), and mixtures thereof. [0044] 1.0.33. Any
of the preceding compositions comprising at least one humectant.
[0045] 1.0.34. Any of the preceding compositions comprising at
least one humectant selected from glycerin, sorbitol, propylene
glycol, and combinations thereof, e.g., in a total amount of
10-40%. [0046] 1.0.35. Any of the preceding compositions comprising
polymer films. [0047] 1.0.36. Any of the preceding compositions
comprising flavoring, fragrance and/or coloring. [0048] 1.0.37. Any
of the preceding compositions comprising at least 50% water. [0049]
1.0.38. Any of the preceding compositions comprising an
antibacterial agent selected from halogenated diphenyl ether (e.g.
triclosan), herbal extracts and essential oils (e.g., rosemary
extract, tea extract, magnolia extract, thymol, menthol,
eucalyptol, geraniol, carvacrol, citral, hinokitol, catechol,
methyl salicylate, epigallocatechin gallate, epigallocatechin,
gallic acid, miswak extract, sea-buckthorn extract), bisguanide
antiseptics (e.g., chlorhexidine, alexidine or octenidine),
quaternary ammonium compounds (e.g., cetylpyridinium chloride
(CPC), benzalkonium chloride, tetradecylpyridinium chloride (TPC),
N-tetradecyl-4-ethylpyridinium chloride (TDEPC)), phenolic
antiseptics, hexetidine, octenidine, sanguinarine, povidone iodine,
delmopinol, salifluor, other metal ions (e.g., zinc salts, for
example zinc citrate, stannous salts, copper salts, iron salts),
sanguinarine, propolis and oxygenating agents (e.g., hydrogen
peroxide, buffered sodium peroxyborate or peroxycarbonate),
phthalic acid and its salts, monoperthalic acid and its salts and
esters, ascorbyl stearate, oleoyl sarcosine, alkyl sulfate, dioctyl
sulfosuccinate, salicylanilide, domiphen bromide, delmopinol,
octapinol and other piperidino derivatives, nicin preparations,
chlorite salts; and mixtures of any of the foregoing. [0050]
1.0.39. Any of the preceding compositions comprising an
antioxidant, e.g., selected from the group consisting of Co-enzyme
Q10, PQQ, Vitamin C, Vitamin E, Vitamin A, anethole-dithiothione,
and mixtures thereof. [0051] 1.0.40. Any of the preceding
compositions comprising a whitening agent. [0052] 1.0.41. Any of
the preceding compositions comprising a whitening agent selected
from a whitening active selected from the group consisting of
peroxides, metal chlorites, perborates, percarbonates, peroxyacids,
hypochlorites, and combinations thereof [0053] 1.0.42. Any of the
preceding compositions further comprising hydrogen peroxide or a
hydrogen peroxide source, e.g., urea peroxide or a peroxide salt or
complex (e.g., such as peroxyphosphate, peroxycarbonate, perborate,
peroxysilicate, or persulphate salts; for example calcium
peroxyphosphate, sodium perborate, sodium carbonate peroxide,
sodium peroxyphosphate, and potassium persulfate), or hydrogen
peroxide polymer complexes such as hydrogen peroxide-polyvinyl
pyrrolidone polymer complexes. [0054] 1.0.43. Any of the preceding
compositions further comprising an agent that interferes with or
prevents bacterial attachment, e.g., solbrol or chitosan. [0055]
1.0.44. Any of the preceding compositions further comprising a
physiologically acceptable potassium salt, e.g., potassium nitrate
or potassium chloride, in an amount effective to reduce dentinal
sensitivity. [0056] 1.0.45. Any of the preceding compositions
comprising from 0.01% to 1% of a physiologically acceptable
potassium salt, e.g., potassium nitrate and/or potassium chloride.
[0057] 1.0.46. Any of the preceding compositions effective upon
application to the oral cavity, e.g., by rinsing, optionally in
conjunction with brushing, to (i) reduce or inhibit formation of
dental caries, (ii) reduce, repair or inhibit pre-carious lesions
of the enamel, e.g., as detected by quantitative light-induced
fluorescence (QLF) or electrical caries measurement (ECM), (iii)
reduce or inhibit demineralization and promote remineralization of
the teeth, (iv) reduce hypersensitivity of the teeth, (v) reduce or
inhibit gingivitis, (vi) promote healing of sores or cuts in the
mouth, (vii) reduce levels of acid producing bacteria, (viii) to
increase relative levels of arginolytic bacteria, (ix) inhibit
microbial biofilm formation in the oral cavity, (x) raise and/or
maintain plaque pH at levels of at least pH 5.5 following sugar
challenge, (xi) reduce plaque accumulation, (xii) treat, relieve or
reduce dry mouth, (xiii) clean the teeth and oral cavity (xiv)
reduce erosion, (xv) prevents stains and/or whiten teeth, (xvi)
immunize the teeth against cariogenic bacteria; and/or (xvii)
promote systemic health, including cardiovascular health, e.g., by
reducing potential for systemic infection via the oral tissues.
[0058] 1.0.47. A composition obtained or obtainable by combining
the ingredients as set forth in any of the preceding
compositions.
[0059] Levels of active ingredients will vary based on the nature
of the delivery system and the particular active. For example, the
zinc salt may be present at levels from, e.g., 0.05 to 2 wt %,
e.g., 0.1 to 1 wt %. Fluoride may be present at levels of, e.g., 25
to 250 ppm, or up to 10.times. higher for a professional or
prescription treatment product. Levels of additional antibacterial
will vary similarly, depending on the agent used. For example, a
triclosan mouthrinse may contain, e.g., 0.03 wt % triclosan.
[0060] In another embodiment, the invention encompasses a method to
improve oral health comprising applying an effective amount of the
oral composition of any of the embodiments set forth above to the
oral cavity of a subject in need thereof, e.g., a method to [0061]
i. reduce or inhibit formation of dental caries, [0062] ii. reduce,
repair or inhibit early enamel lesions, e.g., as detected by
quantitative light-induced fluorescence (QLF) or electrical caries
measurement (ECM), [0063] iii. reduce or inhibit demineralization
and promote remineralization of the teeth, [0064] iv. reduce
hypersensitivity of the teeth, [0065] v. reduce or inhibit
gingivitis, [0066] vi. promote healing of sores or cuts in the
mouth, [0067] vii. inhibit microbial biofilm formation in the oral
cavity, [0068] viii. raise and/or maintain plaque pH at levels of
at least pH 5.5 following sugar challenge, [0069] ix. reduce plaque
accumulation, [0070] x. treat dry mouth, [0071] xi. enhance
systemic health, including cardiovascular health, e.g., by reducing
potential for systemic infection via the oral tissues, [0072] xii.
whiten teeth, [0073] xiii. reduce erosion of the teeth, [0074] xiv.
immunize (or protect) the teeth against cariogenic bacteria and
their effects, and/or [0075] xv. clean the teeth and oral
cavity.
[0076] The invention further comprises the use of any of
methylisothiazolinone, sodium benzoate, potassium sorbate and
combinations thereof in the manufacture of a Composition of the
Invention, e.g., for use in any of the indications set forth in the
above method.
[0077] The compositions of the present invention comprise a
hydrophilic and a hydrophobic phase, and a hydrotrope component
which when mixed form a temporary oil-in-water emulsion, which
breaks down and separates back into the hydrophobic and hydrophilic
phases within 5 seconds to one hour following mixing. It has been
surprisingly determined that the separation of the hydrophilic and
hydrophobic phases is complete, e.g., with no emulsion existing
between the two phases. Without intending to be bound by theory, it
is believed that the high HLB of the hydrophobic phase allows for
the complete separation of the two phases.
[0078] The hydrophobic phase of the composition of the present
invention may contain any orally acceptable hydrophobic liquid,
e.g., generally recognized as safe. Such materials are known in the
art, and may include isopropyl myristate, liquid paraffin (mineral
oil), edible oils such as olive oil, corn oil, coconut oil, soybean
oil, and combinations thereof. A preferred hydrophobic phase
comprises liquid paraffin, isopropyl myristate. Preferably, the
hydrophobic phase has a HLB of from 7 to 12, e.g., 10.
[0079] The hydrophilic phase of the compositions of the present
invention are aqueous based, e.g., having from 40% to 95% by weight
water. Other useful materials may also include orally acceptable
alcohols, humectants, or polymers. A humectant on a pure humectant
basis, generally includes 10% to 50% in one embodiment or 15% to
25% in another embodiment by weight of the mouth wash composition.
The hydrophilic phase may optionally include one or more polymers,
e.g., in the hydrophilic phase, such as polyvinylmethyl ether
maleic acid copolymers, polysaccharides (e.g. cellulose
derivatives, for example carboxymethyl cellulose, or polysaccharide
gums, for example xanthan gum or carrageenan gum). The compositions
of the present invention may contain an orally acceptable
polyvinylmethylether/maleic anhydride (PVME/MA) copolymer. The
PVME/MA copolymer is present from 0.1% to 20%, for example 0.5% to
10% by weight. Generally the methyl vinyl ether to maleic anhydride
ratio in the copolymer is 1:4 to 4:1, and the copolymer has an
average molecular weight of 30,000 to 1,000,000, for example 30,000
to 500,000. Preferred PVME/MA copolymers include those under the
GANTREZ brand from ISP (Wayne, N.J.). The PVME/MA copolymer may
also act as an antibacterial enhancing agent if present in an
antibacterial enhancing effective amount.
[0080] Hydrotropes are known in the art, and include compounds that
solubilizes hydrophobic compounds in aqueous solutions. Hydrotropes
are low molecular weight amphiphilic compounds which resemble
surfactants in as much as they have hydrophilic groups, and, in
surfactant terms, what maybe described as a low molecular weight
hydrophobe. The hydrophilic group is may be attached to an organic
moiety that is too short a group to confer true surface active
properties. Hydrotropes useful in the present invention may include
aromatic sulfonates, aromatic phosphate esters, di and
polycarboxylates, polyglycols, and alcohols, including polyhydric
alcohols. Hydrotropes useful in the present invention have a HLB
value of from 7 to 18. Although any hydrotrope may be useful in the
present invention (preferably GRAS), the hydrotrope may have a HLB
value similar to that of the hydrophobic phase, and thus, the exact
hydrotrope useful in the compositions will be dependent upon the
composition of the hydrophobic phase. Preferably, the HLB of the
coupling system is greater than the HLB of the hydrophobic phase,
e.g., 10%, 15%, 20%, or 30% greater than the HLB of the hydrophobic
phase. Methods of determining HLB is well known to those of skill
in the art. The hydrotrope component in the present invention
comprises one or more polyglycols and/or polyhydric alcohols,
preferably a diol and/or a triol. Preferably, the coupling system
comprises glycerine and propylene glycol. The exact ratio of
glycerine and propylene glycol in the coupling system will depend
on the desired HLB of the hydrotrope component of the present
invention. As the hydrotrope lacks surfactant properties, the
dispersion of the oil phase in the water is not thermodynamically
stable, and an emulsion formed by mixing the two phases reverts
back into separate and distinct phases immediately following
mixing.
[0081] The compositions of the present invention incorporate one or
more surfactants which are known in the art. Suitable surfactants
include those which are reasonably stable throughout a wide pH
range, for example, anionic, cationic, nonionic or zwitterionic
surfactants. Preferred surfactants are nonionic surfactants.
Preferably, the amount of surfactant in the compositions of the
present invention is reduced to minimize the dispersion of the
hydrophobic phase in the hydrophilic phase in the creation of
emulsions which do not separate within 2 minutes from mixing the
phases. It has been surprisingly found that minimizing the
surfactant content and the presence of hydrotropes allows for
efficient separation of the two phases. In one embodiment of the
present invention, the oral compositions are free, or substantially
free of surfactants, especially anionic, cationic, and zwitterionic
surfactants. Nonionic surfactants may be use in limited quantities
in the present invention. Such nonionic surfactants may be defined
as compounds produced by the condensation of alkylene oxide groups
(hydrophilic in nature) with an organic hydrophobic compound which
may be aliphatic or alkylaromatic in nature. Examples of suitable
nonionic surfactants include, but are not limited to, the
Pluronics, polyethylene oxide condensates of alkyl phenols,
products derived from the condensation of ethylene oxide with the
reaction product of propylene oxide and ethylene diamine, ethylene
oxide condensates of aliphatic alcohols, long chain tertiary amine
oxides, long chain tertiary phosphine oxides, long chain dialkyl
sulfoxides and mixtures of such materials. The compositions of the
present invention may contain from 0.0001% to 0.01% by weight of a
surfactant.
[0082] The compositions of the invention are intended for topical
use in the mouth and so salts for use in the present invention
should be safe for such use, in the amounts and concentrations
provided. Suitable salts include salts known in the art to be
pharmaceutically acceptable salts are generally considered to be
physiologically acceptable in the amounts and concentrations
provided. Physiologically acceptable salts include those derived
from pharmaceutically acceptable inorganic or organic acids or
bases, for example acid addition salts formed by acids which form a
physiological acceptable anion, e.g., hydrochloride or bromide
salt, and base addition salts formed by bases which form a
physiologically acceptable cation, for example those derived from
alkali metals such as potassium and sodium or alkaline earth metals
such as calcium and magnesium. Physiologically acceptable salts may
be obtained using standard procedures known in the art, for
example, by reacting a sufficiently basic compound such as an amine
with a suitable acid affording a physiologically acceptable
anion.
[0083] Fluoride Ion Source:
[0084] The oral care compositions may further include one or more
fluoride ion sources, e.g., soluble fluoride salts. A wide variety
of fluoride ion-yielding materials can be employed as sources of
soluble fluoride in the present compositions. Examples of suitable
fluoride ion-yielding materials are found in U.S. Pat. No.
3,535,421, to Briner et al.; U.S. Pat. No. 4,885,155, to Parran,
Jr. et al. and U.S. Pat. No. 3,678,154, to Widder et al.,
incorporated herein by reference. Representative fluoride ion
sources include, but are not limited to, stannous fluoride, sodium
fluoride, potassium fluoride, sodium monofluorophosphate, sodium
fluorosilicate, ammonium fluorosilicate, amine fluoride, ammonium
fluoride, and combinations thereof. In certain embodiments the
fluoride ion source includes stannous fluoride, sodium fluoride,
sodium monofluorophosphate as well as mixtures thereof. Where the
formulation comprises calcium salts, the fluoride salts are
preferably salts wherein the fluoride is covalently bound to
another atom, e.g., as in sodium monofluorophosphate, rather than
merely ionically bound, e.g., as in sodium fluoride.
Flavoring Agents
[0085] The oral care compositions of the invention may also include
a flavoring agent. Flavoring agents which are used in the practice
of the present invention include, but are not limited to, essential
oils and various flavoring aldehydes, esters, alcohols, and similar
materials, as well as sweeteners such as sodium saccharin. Examples
of the essential oils include oils of spearmint, peppermint,
wintergreen, sassafras, clove, sage, eucalyptus, marjoram,
cinnamon, lemon, lime, grapefruit, and orange. Also useful are such
chemicals as menthol, carvone, and anethole. Certain embodiments
employ the oils of peppermint and spearmint.
[0086] The flavoring agent is incorporated in the oral composition
at a concentration of 0.01 to 1% by weight.
Chelating and Anti-Calculus Agents
[0087] The oral care compositions of the invention also may
optionally include one or more chelating agents able to complex
calcium found in the cell walls of the bacteria. Binding of this
calcium weakens the bacterial cell wall and augments bacterial
lysis.
[0088] One group of agents suitable for use as chelating or
anti-plaque agents in the present invention are the soluble
pyrophosphates. The pyrophosphate salts used in the present
compositions can be any of the alkali metal pyrophosphate salts. In
certain embodiments, salts include tetra alkali metal
pyrophosphate, dialkali metal diacid pyrophosphate, trialkali metal
monoacid pyrophosphate and mixtures thereof, wherein the alkali
metals are sodium or potassium. The salts are useful in both their
hydrated and unhydrated forms. An effective amount of pyrophosphate
salt useful in the present composition is generally enough to
provide at least 0.5 wt. % pyrophosphate ions, 0.9-3 wt. %.
[0089] These compounds also contribute to preservation of the
compositions by lowering water activity.
Enzymes
[0090] The oral care compositions of the invention may also
optionally include one or more enzymes. Useful enzymes include any
of the available proteases, glucanohydrolases, endoglycosidases,
amylases, mutanases, lipases and mucinases or compatible mixtures
thereof. In certain embodiments, the enzyme is a protease,
dextranase, endoglycosidase and mutanase. In another embodiment,
the enzyme is papain, endoglycosidase or a mixture of dextranase
and mutanase. Additional enzymes suitable for use in the present
invention are disclosed in U.S. Pat. No. 5,000,939 to Dring et al.,
U.S. Pat. No. 4,992,420; U.S. Pat. No. 4,355,022; U.S. Pat. No.
4,154,815; U.S. Pat. No. 4,058,595; U.S. Pat. No. 3,991,177; and
U.S. Pat. No. 3,696,191 all incorporated herein by reference. An
enzyme of a mixture of several compatible enzymes in the current
invention constitutes 0.002% to 2.0% in one embodiment or 0.05% to
1.5% in another embodiment or in yet another embodiment 0.1% to
0.5%.
Water
[0091] Water is present in the oral compositions of the invention.
Water, employed in the preparation of commercial oral compositions
should be deionized and free of organic impurities. Water commonly
makes up the balance of the compositions and includes 10% to 90%,
e.g., 40% to 70% by weight of the oral compositions. This amount of
water includes the free water which is added plus that amount which
is introduced with other materials such as with sorbitol or any
components of the invention.
Humectants
[0092] Within certain embodiments of the oral compositions, it is
also desirable to incorporate a humectant to reduce evaporation and
also contribute towards preservation by lowering water activity.
Certain humectants can also impart desirable sweetness or flavor to
compositions. The humectant, on a pure humectant basis, generally
includes 15% to 70% in one embodiment or 30% to 65% in another
embodiment by weight of the composition.
[0093] Suitable humectants include edible polyhydric alcohols such
as glycerine, sorbitol, xylitol, propylene glycol as well as other
polyols and mixtures of these humectants. Mixtures of glycerine and
sorbitol may be used in certain embodiments as the humectant
component of the compositions herein.
[0094] The present invention in its method aspect involves applying
to the oral cavity a safe and effective amount of the compositions
described herein.
[0095] The compositions and methods according to the invention are
useful to a method to protect the teeth by facilitating repair and
remineralization, in particular to reduce or inhibit formation of
dental caries, reduce or inhibit demineralization and promote
remineralization of the teeth, reduce hypersensitivity of the
teeth, and reduce, repair or inhibit early enamel lesions, e.g., as
detected by quantitative light-induced fluorescence (QLF) or
electronic caries monitor (ECM).
[0096] Enhancing oral health also provides benefits in systemic
health, as the oral tissues can be gateways for systemic
infections. Good oral health is associated with systemic health,
including cardiovascular health. The compositions and methods of
the invention are thus useful to enhance systemic health, including
cardiovascular health.
[0097] As used throughout, ranges are used as shorthand for
describing each and every value that is within the range. Any value
within the range can be selected as the terminus of the range. In
addition, all references cited herein are hereby incorporated by
reference in their entireties. In the event of a conflict in a
definition in the present disclosure and that of a cited reference,
the present disclosure controls. It is understood that when
formulations are described, they may be described in terms of their
ingredients, as is common in the art, notwithstanding that these
ingredients may react with one another in the actual formulation as
it is made, stored and used, and such products are intended to be
covered by the formulations described.
[0098] The following examples further describe and demonstrate
illustrative embodiments within the scope of the present invention.
The examples are given solely for illustration and are not to be
construed as limitations of this invention as many variations are
possible without departing from the spirit and scope thereof.
Various modifications of the invention in addition to those shown
and described herein should be apparent to those skilled in the art
and are intended to fall within the appended claims.
Example 1
Mouthwashes
[0099] Formulations of the invention are prepared with the
following ingredients, weight percentages given with respect to the
final dual phase formulation:
TABLE-US-00001 Phase A Phase B Ingredients (hydrophobic)
(hydrophilic) Glycerin -- 7.5 Mineral oil 12 -- Sodium Fluoride --
0.05 Sodium Saccharin -- 0.08 Citric Acid--Anhydrous -- 0.01
Monosodium Phosphate anhydrous -- 0.05 Surfactant -- 0.1 Flavor 1.1
-- Dye 0.00012 0.004 Potassium Sorbate -- 0.1 Sodium Benzoate --
0.11 Cetyl Pyridinium Chloride -- 0.05 Water -- Balance pH N/A
5.5
[0100] To optimize the preservative system, different preservatives
are substituted for potassium sorbate and/or sodium bezoate in the
above formulation, and the characteristics of the formulation
tested for antimicrobial efficacy of the hydrophilic phase, flavor
impact, and aesthetics impact.
[0101] The Antimicrobial Preservation Effectiveness Test is used to
determine the antimicrobial preservation effectiveness of
water-based product formulations by means of a double challenge
test. Products are developed to withstand microbial challenges
introduced by normal consumer use. The test is run on an aged
sample (13 weeks, 40.degree. C.). The test uses two pools of
microorganisms: bacteria/yeast and mold. The product is challenged
at a 1% level at day 0 and at day 7. Reduction of the inoculum is
monitored over a 28 day period. The following are the acceptance
criteria for mouth wash formulas. [0102] Bacteria and Yeast must
show a 99.9% reduction (3 logs) of the bacterial inoculum as
determined by plate count on day 7 following each inoculation. No
increase after day 7 of the second inoculation and for the
remainder of the test within normal variation of the data. [0103]
Mold must show a 90.0% reduction (1 log) of the mold inoculum as
determined by the plate count on day 14 following the second
inoculation (day 21). No increase from day 14 to day 21 of the
second inoculation of the test within normal variation of the
data.
[0104] Flavor is evaluated via an organoleptic evaluation by
trained flavorists.
[0105] Aesthetics are evaluated by a visual comparison to a control
sample having the same types and levels of colorant and flavoring
agents.
[0106] Results of the comparative testing are as follows, where a "
" indicates criteria are met, and an "X" indicates criteria are not
met.
TABLE-US-00002 0.11% Na Na benzoate Na benzoate benzoate/ 0.11% Na/
@ @ 0.1% 0.001% Preservative 0.44% 0.11% K sorbate MIT Micro
robustness X In vitro eff. Flavor impact X Aesthetics impact
Sodium benzoate provided acceptable microbial control alone at
0.44%, but this level had an adverse effect on flavor. When the
amount of sodium benzoate was reduced, the level of microrobustness
was reduced. The ideal formulation was a combination of sodium
bezoate at 0.11% with low levels of potassium sorbate (0.1%) or
methylisothiazolinone (MIT) (0.001%), which had good antimicrobial
efficacy without detrimental effects on flavor or appearance of
product.
* * * * *